Platelets may serve up biomarkers

Biomarkers, biological measurements that identify or “mark” the presence of disease, are nothing new to medicine, as exemplified by the routine use of CK-MB and troponin measurements to identify patients who have suffered a heart attack. However, the current “omics” revolution, which allows the simultaneous measurement of hundreds or thousands of molecules from a single sample, has reinvigorated the search for novel biomarkers for a variety of diseases.

In this issue of Blood, Cervi and colleagues used a proteomic technique known as mass spectroscopy to examine the platelet proteome of mice injected with a variety of tumor cells, compared with saline-injected controls. Among the proteins that differed in tumor-bearing mouse platelets, these investigators identified platelet factor 4 (PF4) as a biomarker of a variety of tumor types, including liposarcoma, osteosarcoma, and adenocarcinoma. A significant change in plasma PF4 was not detected.

These studies challenge us to look beyond traditional fluid sources of disease markers (plasma, urine, and cerebrospinal fluid). By examining platelets, Cervi et al were able to identify PF4 as a cancer-associated protein, even though PF4 levels do not change in the plasma. The lack of value of plasma PF4 as a biomarker in this study is not unexpected, as PF4 readily cleared from the plasma by binding to abundant gycosaminoglycans in the vasculature,¹  highlighting the value of nontraditional biological samples to aid in the diagnosis of disease.

While Cervi et al used mass spectroscopy to identify and quantitate PF4 as a tumor biomarker, this technology is not widely available in clinical laboratories. The study demonstrates that increases in platelet PF4 can also be measured using the much simpler and more accessible method of ELISA. The use of ELISA in place of mass spectroscopy enhances our ability to validate the usefulness of platelet PF4 as a biomarker for early detection of cancer.

Although it is not a requirement, since biomarkers may simply have a disease association, biomarkers may have pathophysiological relevance to the disease that they identify. In this case, increases in platelet PF4 may be involved in tumor growth, as PF4 is known to regulate angiogenesis^2,3  and may inhibit tumor growth.⁴  As such, PF4 in platelets represents not only a potentially useful cancer biomarker, but a potential target for early cancer therapy as well.